State-dependent cross-inhibition between transmitter-gated cation channels

Baljit S. Khakh (), Xiaoping Zhou, Jason Sydes, James J. Galligan and Henry A. Lester
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Baljit S. Khakh: California Institute of Technology
Xiaoping Zhou: Michigan State University
Jason Sydes: California Institute of Technology
James J. Galligan: Michigan State University
Henry A. Lester: California Institute of Technology

Nature, 2000, vol. 406, issue 6794, 405-410

Abstract: Abstract Transmitter-gated cation channels are detectors of excitatory chemical signals at synapses in the nervous system1. Here we show that structurally distinct α3β4 nicotinic and P2X2 channels influence each other when co-activated. The activation of one channel type affects distinct kinetic and conductance states of the other, and co-activation results in non-additive responses owing to inhibition of both channel types. State-dependent inhibition of nicotinic channels is revealed most clearly with mutant P2X2 channels, and inhibition is decreased at lower densities of channel expression. In synaptically coupled myenteric neurons, nicotinic fast excitatory postsynaptic currents are occluded during activation of endogenously co-expressed P2X channels. Our data provide a molecular basis and a synaptic context for cross-inhibition between transmitter-gated channels.

Date: 2000
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DOI: 10.1038/35019066

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